Living organisms require oxygen supply and removal of CO2 to maintain their life and activity. In land based animals this is achieved by the respiratory system that pumps air into and out of the lungs and enables the required gas exchange between the inspired air and the circulating blood. In general terms the respiratory process is based on the passage of air through the mouth to the alveoli. Once air progresses through the mouth or nose, it travels through the oropharynx, nasopharynx, the larynx, the trachea, and a progressively subdividing system of bronchi and bronchioles of smaller and smaller diameter until it finally reaches the alveoli where the gas exchange of carbon dioxide and oxygen takes place.
The drawing and expulsion of air (ventilation or breathing) is driven by muscular action. Breathing is largely driven by the muscular diaphragm at the bottom of the thorax. Contraction of the diaphragm pulls the bottom of the cavity in which the lung is enclosed downward, increasing volume and thus decreasing pressure, causing air to flow into the airways. During normal breathing, expiration is passive and no muscles are contracted (the diaphragm relaxes). The rib cage itself is also able to expand and contract to some degree, through the action of other respiratory and accessory respiratory muscles. As a result, air is transported into or expelled out of the lungs. Air flow is dependent on the pressure gradient (between the alveoli and ambient air) and the resistance to flow in the described pathways (bronchi, bronchioles, etc.).
In a variety of diseases, for example COPD (chronic obstructive pulmonary disease) and specifically emphysema and asthma, the airways are narrowed such that the resistance to air flow (R) is increased resulting in flow limitation. Under such conditions and especially during exercise etc. the patient may suffer from lack of oxygen, increase of the level of blood CO2 and the corresponding pH changes, etc. Note that in the US alone the number of patients suffering from the above is in excess of 20 million.
Pulmonary function tests (such as those described in Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (NIH Publication Number 08-5846 ed.). National Institutes of Health. 2007) are commonly used to diagnose and evaluate the state of air flow restrictive diseases. These tests include means for direct measurement of R. This measurement involves placement of the patient in a hermetically closed chamber while having him breathe through a pipe leading to the outside. This is an expensive and inconvenient test and only few specialized clinics carry it out. The alternative method “interrupted flow” proposed in Reassessment of the interruption technique for measuring flow resistance in humans. Liistro G, St{hacek over (a)}nescu D, Rodenstein D, Verner C.; Reassessment of the interruption technique for measuring flow resistance in humans. J Appl Physiol. 1989 September; 67(3):933-7 was proved inaccurate.